共查询到20条相似文献,搜索用时 31 毫秒
1.
T.M.A. Elattar A.S. Virji 《Prostaglandins, leukotrienes, and essential fatty acids》1997,56(6):461-465
Four cyclopentenone prostaglandins (CPPGs) and PGE2 caused significant dose-dependent inhibition in growth of human oral squamous carcinoma cells (SCC-15). The rank order of their potency was PGJ2>PGA1>16, 16-dimethyl PGA1>PGA2>PGE2. In a follow-up experiment it was found that the mean per cent inhibition in cell growth by PGJ2 and Δ12-PGJ2 at 10−5 M was 61.22 and 63.81, while that of 5-fluorouracil and methotrexate was 36.67 and 38.86, respectively. Δ12-PGJ2 and PGJ2 induced significant dose-dependent inhibition in nuclear DNA synthesis (i.e. cell proliferation). Combining vitamin E succinate with lower concentrations of CPPGs enhanced significantly their inhibitory effect on nuclear DNA synthesis of cancer cells. 相似文献
2.
The effect of 8 prostaglandins (PG) on growth and sulfate incorporation by monolayer and spinner-cultured rabbit articular chondrocytes has been measured. PGA1, PGB1, PGE1 and PGE2 reduced synthesis of sulfated glycosaminoglycans (GAG) but the PGF series did not. PGA1 was the most potent, being effective at a concentration of 2.5 μg/ml [6.8 μM] while the others required 25 μg/ml. These compounds had no effect on degradation of GAG. All 8 PGs augmented growth slightly but significantly at 2.5 μg/ml. At the higher concentration, PGA1 was highly cytotoxic, and PGB1 as well as PGE2 reduced cell growth. The cytotoxicity of PGA1 was also observed in two additional types of cultured connective tissue cells, but the inhibition of sulfated-GAG synthesis by PGA1 and PGB1 was confined to the chondrocytes. The response of cultured chondrocytes to exogenous PGs, albeit at apparently unphysiologically high concentrations, together with other evidence, suggests that these compounds may conceivably play a direct role in cartilage metabolism in vivo. 相似文献
3.
M. Gabriella Santoro Arrigo Benedetto Bernard M. Jaffe 《Prostaglandins & other lipid mediators》1979,17(5):719-727
The effect of different prostaglandins and prostaglandin-metabolites on the growth and differentiation of Friend erythroleukemia cells (FLC) was evaluated. The prostaglandin-metabolites, thromboxane B2 and 6-keto PGF1α, were completely inactive, while PGE1 inhibited slightly and PGF2α stimulated the replication of FLC. PGA1 was found to be the most active compound. It profoundly inhibited the replication of both DMSO-treated and undifferentiated FLC. Most importantly, PGA1 alone induced differentiation in FLC, stimulating hemoglobin production over a five-day period. PGA1-stimulated differentiation was completely suppressed by the addition of 10−6M hydrocortisone. Finally, treatment of DMSO-differentiated cells with PGA1 (but no DMSO) prevented the return to the undifferentiated state. 相似文献
4.
George S. Eisenbarth David K. Wellman Harold E. Lebovitz 《Biochemical and biophysical research communications》1974,60(4):1302-1308
The effects of various prostaglandins (PG) on the in vitro synthesis of macromolecules by two transplantable chondrosarcomas were studied. Prostaglandin A1 markedly inhibited the incorporation of radioactive precursors into chondromucoprotein, total protein, RNA and DNA of both a well differentiated rat chondrosarcoma and a poorly differentiated murine chondrosarcoma. PGE1 and PGF1α had no effects on the synthesis of macromolecules by either tumor. PGA1 inhibitory effects occurred over a dose range of 1 to 25 μg/ml. PGA1 had no effect on the synthesis of macromolecules by liver. The data indicate that malignant transformation of cartilage cells does not alter their responsiveness to PGA1. 相似文献
5.
K V Honn J R Dunn L R Morgan M Bienkowski L J Marnett 《Biochemical and biophysical research communications》1979,87(3):795-801
PGA1 and PGA2 significantly depressed melanoma cell DNA synthesis and cell proliferation in a dose related fashion. Inhibition of DNA synthesis was rapid in onset (0.5–1 hr) and sustained (12 hr). This was not due to general cytotoxicity or depression of substrate uptake. Comparison with known cancer chemotherapeutic agent revealed PGA1 and PGA2 effectiveness on a molar basis exceeded that of Adriamycin, cyclophosphamide and hydroxyurea. Actinomycin D, Mutamycin and 5-fluorouracil were more potent than PGA1 and PGA2 but consideration of their toxicities may outweigh this point. The findings suggest that the A series prostaglandins or their analogs may be efficacious in cancer chemotherapy. 相似文献
6.
I. V. Fedoseeva N. N. Varakina T. M. Rusaleva G. B. Borovskii E. G. Rikhvanov V. K. Voinikov 《Microbiology》2010,79(2):153-159
Effect of calcium ions on heat tolerance of Saccharomyces cerevisiae and on the induction of Hsp104 synthesis by this microorganism was studied. Short-term (30 min) treatment with CaCl2 at 30°C enhanced the heat tolerance to the lethal heat shock (50°C); the synthesis of Hsp104 was induced as well. The effect
of Ca2+ on the heat tolerance and Hsp104 synthesis was shown to be ion-specific and was inhibited by LaCl3, which is known to block calcium ion channels on the cytoplasmic membrane. The effect of Ca2+ depended on the potential of the inner mitochondrial membrane. When the cells were treated with sodium azide, which reduced
the electrochemical potential, the effect of calcium both on heat tolerance and Hsp104 synthesis was suppressed. Depending
on the concentration of exogenous Ca2+ and the ambient conditions, calcium ions may either induce or inhibit the expression of the stress genes and cell viability. 相似文献
7.
We have recently reported that cartilage has two sites for prostaglandin (PG) action. One site (S1) is stimulated by PGA1, PGE1 and PGF1α and elevates tissue cyclic 3′5′adenosine monophosphate (cAMP). A second site (S2) is activated by PGA1 (but not PGE1 or PGF1α) and inhibits the synthesis of cartilage macromolecules. The present study is an investigation of the effects of PGB1 on embryonic chicken cartilage chondromucoprotein synthesis in vitro. PGB1 was found to inhibit chondromucoprotein synthesis with an apparent affinity for S2 which was similar to that of PGA1. The maximal inhibition produced by PGB1 was, however, approximately one-half the maximal inhibition caused by PGA1. Studies of the combined effects of PGB1 and PGA1 were consistent with the hypothesis that both classes of prostaglandins act at a common site (S2) with about equal affinity but that PGB1 has a lower intrinsic activity than PGA1. Similar studies of the combined effects of PGE1 or PGF1α with PGA1 indicate that neither PGE1 nor PGF1α binds significantly to S2. An independent effect of PGB1 to activate S1 and elevate tissue cAMP was also found. 相似文献
8.
Both the psychrophile Aquaspirillum arcticum and the psychrotroph Bacillus psychrophilus were found to acquire thermotolerance when either heat shocked or treated with nalidixic acid; two conditions which also resulted in the induction of heat shock proteins and/or stress proteins and also cell filamentation. The possible relatedness of acquisition of thermotolerance and cell filamentation was examined by inhibiting cell filamentation with 1.5% KCl. A. arcticum cells which were heat shocked in the presence of KCl did not become filamentous nor acquire thermotolerance suggesting that these two responses may be related. On the other hand, when cells of B. psychrophilus were treated in a similar fashion, they also were prevented from cell filamentation but their ability to become thermotolerant was unaffected. When A. arcticum cells were heat shocked in the presence of chloramphenicol, heat shock protein synthesis was inhibited but not the acquistion of thermotolerance. Similar experiments with B. psychrophilus revealed that partial induction of heat shock proteins still occurred; however, no thermotolerance was exhibited.Abbreviations hsp(s)
heat shock proteins(s)
- SEM
standard error of the mean 相似文献
9.
Beatriz Garzón Javier Gayarre Severine Gharbi Beatriz Díez-Dacal Francisco J. Sánchez-Gómez John F. Timms Dolores Pérez-Sala 《Chemico-biological interactions》2010,183(1):212-221
The cyclopentenone prostaglandin (cyPG) PGA1 displays potent anti-proliferative and anti-inflammatory effects. Therefore, PGA1 derivatives are being studied as therapeutic agents. One major mechanism for cyPG action is the modification of protein cysteine residues, the nature of the modified proteins being highly dependent on the structure of the cyPG. Biotinylated cyPGs may aid in the proteomic identification of cyPG targets of therapeutic interest. However, for the identified targets to be relevant it is critical to assess whether biotinylated cyPGs retain the desired biological activity. Here we have explored the anti-inflammatory, anti-proliferative and cell stress-inducing effects of a biotinylated analog of PGA1 (PGA1-biotinamide, PGA1-B), to establish its validity to identify cyPG–protein interactions of potential therapeutic interest. PGA1 and PGA1-B displayed similar effects on cell viability, Hsp70 and heme oxygenase-1 induction and pro-inflammatory gene inhibition. Remarkably, PGA1-B did not activate PPAR. Therefore, this biotinylated analog can be useful to identify PPAR-independent effects of cyPGs. Protein modification and subcellular distribution of PGA1-B targets were cell-type-dependent. Through proteomic and biochemical approaches we have identified a novel set of PGA1-B targets including proteins involved in stress response, protein synthesis, cytoskeletal regulation and carbohydrate metabolism. Moreover, the modification of several of the targets identified could be reproduced in vitro. These results unveil novel interactions of PGA1 that will contribute to delineate the mechanisms for the anti-proliferative and metabolic actions of this cyPG. 相似文献
10.
Sun-Young Lee Ji-Hyun Ahn Kyoung Won Ko Jaetaek Kim Seong Whan Jeong In-Kyung Kim Jin Kim Ho-Shik Kim 《Prostaglandins & other lipid mediators》2010,91(1-2):30-37
HL-60 cells treated by prostaglandin (PG) A2 showed characteristics of apoptosis such as accumulation of hypodiploid and annexin V positive cells, condensed and fragmented nuclei, cytochrome c (Cyt C) release from mitochondria and activation of caspase-1, -2, -3, -7 and -9. PGA2-induced cell death was rescued by inhibitors of caspase-9 and -3, but PGA2-induced Cyt C release was not prevented by caspase inhibitors. During Cyt C release by PGA2, mitochondrial transmembrane potential was maintained and mitochondrial permeability transition pore was not formed. In addition, anti-apoptotic BCL-2 family proteins like BCL-2 and BCL-XL, and ROS scavengers including ascorbic acid and 2,2,6,6-tetramethyl-1-piperidinyloxy were not able to inhibit Cyt C release as well as apoptosis by PGA2. Finally, it was shown that PGA2-induced Cyt C release in vitro from purified mitochondria in the absence of cytosolic components. Furthermore, thiol-containing compounds such as N-acetylcysteine, l-cysteine and monothioglycerol prevented Cyt C release, and hence induction of apoptosis. Taken together, these results suggest that PGA2 activates intrinsic apoptotic pathway by directly stimulating mitochondrial outer membrane permeabilization to release Cyt C, in which thiol-reactivity of PGA2 plays a pivotal role. 相似文献
11.
A rabbit lung preparation, perfused , was used to examine pulmonary metabolism of prostaglandin A1 (PGA1) and to compare the vasoconstrictor actions of PGA1, prostaglandin F2α (PGF2α) and angiotensin II. PGF2α caused significantly more, and angiotensin II significantly less, vasoconstriction than did an equimolar concentration of PGA1. Of three likely PGA1 metabolites only 15-keto-PGA1 had any significant vasoconstrictor action. Furosemide and aminophylline (10?3 M) reduced PGA1, PGF2α or angiotensin II-induced vasoconstruction. Diphloretin phosphate potentiated the vascular effect of angiotensin II. Furosemide (10?3 M) and DPP (9.5 × 10?6 M) significantly reduced pulmonary metabolism of PGA1 while aminophylline (10?3 M) had no effect on this process. Perfusion of the lungs with a hypoxic medium had no effect on PGA1 metabolism. 相似文献
12.
Although acquired thermotolerance has been linked to the induction of heat shock proteins, the molecular mechanism(s) by which cells become resistant to heat is unknown. The present study shows a strong correlation between the survival of cells following heat shock and the rate of recovery of protein, total RNA, and rRNA synthesis. Increasing exposure of CHO cells to 45 degrees C was found to decrease survival and cause a lengthening delay in these synthetic processes. The same reciprocal correlation was seen in thermotolerant cells. As thermotolerance develops, more cells survive a heat challenge and the delay in synthesis decreases. These data argue that enhanced recovery of protein and RNA synthesis is one factor which plays a key role in thermotolerance. The involvement of rRNA synthesis was further investigated by using actinomycin D at 0.1 microgram m1(-1), a concentration at which rRNA synthesis is selectively inhibited. When the drug was present during the recovery from a challenge heat treatment, the survival of thermotolerant cells was approximately 3-fold lower than expected from the mild toxicity of the drug. As this could not be accounted for by an interaction of the drug with the response of cells to single heat treatments, it is concluded that the drug inhibits the expression of thermotolerance in cells which would otherwise express a full degree of thermotolerance. The time and concentration dependence of this effect indicates that the drug acts though inhibition of rRNA synthesis. Therefore, enhanced recovery of RNA synthesis, presumably rRNA synthesis, is identified as one of the mechanisms responsible for enhanced survival of thermotolerant cells following heat shock. 相似文献
13.
C. Favalli E. Garaci M.G. Santoro L. Santucci B.M. Jaffe 《Prostaglandins & other lipid mediators》1980,19(4):587-594
This study evaluated the effects of PGA1 on B-16 melanoma-bearing mice. Intraperitoneal injection of PGA1 (10 μg/day) significantly inhibited the rate of melanoma growth measured both as delay in the rate of appearance and decrease in the tumor volume. In contrast to the diluent control-treated mice, by 17 days, less than half of the PGA1 — treated animals developed measurable (>2mm) subcutaneous tumors. In addition to its effect on tumor size, PGA1 was also effective in stimulating both the humoral and cellular components of the immune response. B-16 tumor-bearing mice were shown to be immunosuppressed, in that they had decreased anti-sRBC hemagglutinin titers, decreased splenic plaque-forming cells, suppressed delayed hypersensitivity responses, and delayed rejection of skin allografts from BALB/c mice. Although, PGA1 had relatively little effect on normal mice, this prostaglandin substantially improved all these immunologic parameters in tumor-bearing animals. 相似文献
14.
Since the renal cortex has recently been shown to be a major site of prostaglandin A1 (PGA1) metabolism, studies were undertaken to isolate and characterize the major metabolites. Homogenates of rabbit cortex (500g) were incubated with 3H-PGA1 (50mg) in the presence of NAD+ (50mg). Acidic lipid extracts were subjected to linear gradient silicic acid chromatography. Six radioactive peaks were recovered, of which peak 4 was unconverted PGA1. The major metabolites (1,3) were further subjected to reversed phase partition chromatography and TLC with and without silver nitrate. Three PGA1 analogs were then synthesized via oxidation of the secondary alcohol group at C-15 by manganese dioxide (15-keto-PGA1). The second compound was synthesized by hydrogenation of 15-keto-PGA1 (15-keto 13, 14-dihydro PGA1). The third compound (13, 14-dihydro PGA1) was obtained by direct catalytic hydrogenation of PGA1. Purification of these substances were achieved by a combination of silicic acid and thin layer chromatography. It was found that metabolite 1 cochromatographed on TLC (AgNO3) with synthesized 15-keto 13, 14-dihydro PGA1. Both compounds were 100 times less potent than PGA1 in lowering rat blood pressure. Metabolite 3 cochromatographed on TLC (AgNO3) with synthesized 13, 14-dihydro PGA1. Both were as potent as PGA1 in lowering rat blood pressure. Metabolites 1 and 3 absorbed UV at 221 nm but not at 280 nm following alkali treatment. These studies suggest that rabbit renal cortex metabolizes PGA1 to what appears to be biologically active 13, 14-dihydro PGA1 and biologically inactive 15-keto 13, 14-dihydro PGA1. It remains possible that the hypotensive effect of PGA1 is the result of its conversion to its biologically active 13, 14-dihydro derivative. 相似文献
15.
M.G. Santoro A. Benedetto S. Zaniratti E. Garaci B.M. Jaffe 《Prostaglandins & other lipid mediators》1983,25(3)
African Green Monkey Kidney cells were shown to normally synthesize immunoreactive PGE1. Infection of these cells with Sendai virus did not alter rates of PGE1 synthesis, while it stimulated interferon production. PGAs, that we have previously shown to be potent inhibitors of Sendai virus replication in this system, at the same dose (4 μg/ml), also strongly inhibited the replication of this virus in HEp-2 cells and in VERO cells, a monkey kidney cell line that does not produce interferon. PGA1 was found to be effective in several cell and virus models, suggesting a broad spectrum of antiviral actions. Finally, we confirmed the observation that PGA1-treatment prevents the establishment of a “carrier state” by Sendai virus, and PGA1-cured cells did not show any sign of persistent infection for periods as long as 110 days after Sendai function. Attempts to cure already established persistently infected cells were only partially successful. 相似文献
16.
Heat shock and ceramide have different apoptotic pathways in radiation induced fibrosarcoma (RIF) cells 总被引:3,自引:0,他引:3
Heat shock induces various cellular responses including inhibition of protein synthesis, production of heat shock proteins (HSPs) and induction of thermotolerance. The molecular mechanisms of the processes have not been well understood. It has been proposed that ceramide formation during heat shock mediates heat shock induced apoptosis. We examined whether C2-ceramide mimicked the cellular response to heat shock in RIF-1 cells and their thermotolerant derivative TR-RIF-1 cells. Discernible effects between heat shock and C2-ceramide treatments were observed in cellular changes such as total protein synthesis, HSP synthesis, stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) activity and PARP cleavage. Heat shock immediately inhibited cellular protein synthesis, which was recovered by synthesizing HSPs first and then whole proteins later. Heat shock also activated SAPK/JNK and increased PARP cleavage in dose-dependent manner. Thermotolerant TR-RIF-1 cells responded to heat shock more insensitively than RIF-1 cells. On the other hand, C2-ceramide treatment did not accompany any changes induced by heat shock. No discernible differences between RIF-1 and TR-RIF-1 cells were observed by C2-ceramide treatment. We tried to figure out how C2-ceramide interacts with cellular membrane and found that exogenous C2-ceramide was incorporated into the outer monolayer and flipped into the inner monolayer of human erythrocytes in ATP-dependent manner. However, the rate of C2-ceramide incorporation was similar in control and thermotolerant cells. In summary, thermotolerant cells are resistant to heat shock induced apoptotic signaling but not resistant, rather sensitive to membrane disturbing C2-ceramide mediated apoptosis. These results suggest that heat shock and ceramide have different signal transduction pathways. 相似文献
17.
Chinese hamster ovary (CHO) cells became thermotolerant after treatment with either heat for 10 min at 45.5 degrees C or incubation in 100 microM sodium arsenite for 1 h at 37 degrees C. Thermotolerance was tested using heat treatment at 45 degrees C or 43 degrees C administered 6-12 h after the inducing agent. At 45 degrees C thermotolerance ratios at 10(-2) isosurvival levels were 4.2 and 3.8 for heat and sodium arsenite, respectively. Recovery from heat damage as measured by resumption of protein synthesis was more rapid in heat-induced thermotolerant cells than in either sodium arsenite-induced thermotolerant cells or nonthermotolerant cells. Differences in inhibition of protein synthesis between heat-induced thermotolerant cells and sodium arsenite-induced thermotolerant cells were also evident after test heating at 43 degrees C for 5 h. At this temperature heat-induced thermotolerant cells were protected immediately from inhibition of protein synthesis, whereas sodium arsenite-induced thermotolerant cells, while initially suppressed, gradually recovered within 24 h. Furthermore, adding cycloheximide during the thermotolerance development period greatly inhibited sodium arsenite-induced thermotolerance (SF less than 10(-6] but not heat-induced thermotolerance (SF = 1.7 X 10(-1] when tested with 43 degrees C for 5 h. Our results suggest that both the development of thermotolerance and the thermotolerant state for the two agents, while similar in terms of survival, differed significantly for several parameters associated with protein synthesis. 相似文献
18.
D Kupfer 《Life sciences》1974,15(4):657-670
The spectral changes associated with the addition of prostaglandins (PGs) to hepatic microsomes from guinea pigs and rats were examined. PGA1, PGA2, PGE1, PGE2, PGF1α and PGF2α when added to guinea pig liver microsomes exhibited type I spectra. The binding affinities as determined from spectral dissociation constants (Ks) were highest with PGA1 and PGA2. With liver microsomes from control or 3-methyl-cholanthrene (MC)-treated rats, PGs did not yield type I spectra; however, in this case a spectrum, designated here as type “II” was at times observed, With microsomes from phenobarbital (Pb)-treated rats only PGA1 and PGA2 yielded type I spectra; again in absence of type I spectrum, a weak type “II” was occasionally observed. The addition of PGA1 and PGA2 to liver microsomes from Pb-treated rats inhibited the microcomal mediated hydroxylation of hexobarbital. The inhibition by PGA1 was competitive; the Ki = 8.2 × 10?4 M was found to be similar in magnitude to the Ks = 7.3 × 10?4 M of PGA1 observed with rat liver microsomes. These observations suggested that PGs particularly of the A series interact with the hepatic microsomal cytochrome P-450 monooxygenase system. 相似文献
19.
The inhibitory effect of various prostaglandin analogues on the anchorage independent growth of murine and human melanoma cells was measured. PGA analogues (which were modified at C-16 and C-18) did not demonstrate any major improvement in activity over PGA alone. These included 16, 16-dimethyl PGA1, 16,16-dimethyl-PGA2, 16,16-dimethyl-18-oxa-PGA2 and trans-δ-2-15-α acetoxy-16,16-dimethyl-18-oxa-11-deoxy-PGE1-methylester. The thromboxane synthetase inhibitor, U51605, demonstrated weak anti-proliferative activity. PGD2 (with a ketone at C-11 versus C-9 for PGA and PGE) was the most potent prostaglandin tested. Cells from melanoma lines displayed species differences in their sensitivities. PGA1 and PGE1 were the most potent inhibitors of the anchorage independent growth of murine melanoma cells. On human melanoma cells PGD2 was the most active prostaglandin, 2–3 times more potent than PGA1; PGE1 was a very weak inhibitor. 相似文献
20.
Hollis J. Hawkins Alan G.E. Wilson Marshall W. Anderson Thomas E. Eling 《Prostaglandins & other lipid mediators》1977,14(2):251-259
We have investigated the uptake and subsequent metabolism of the prostaglandins (PGs) PGE1, PGA1, and PGB1 by rat, guinea pig and rabbit isolated perfused lungs (IPL). Significant species differences were not observed in the uptake or metabolism of any PG on passage through the IPL. However, differences in the uptake of PGA1 and PGB1 and in the metabolism of PGA1 were observed with a given species when the composition of the perfusion medium was varied. The IPL removed minimal amounts (<20% of the supply rate) of PGA1 and PGB1 from the circulation when the perfusate contained 4.5% bovine serum albumin (BSA). In the absence of BSA, however, both PGA1 and PGB1 were substantially removed from circulation (~53% of the supply rate) and PGA1 was also metabolized. The composition of the perfusate had no effect on the uptake and metabolism of PGE1 which was always taken up and metabolized to a greater extent than was PGA1 and PGB1. Thus, the apparent species differences previously reported for the pulmonary biotransformation of PGA can result from differences in the perfusion medium used. Our data suggest that both plasma protein binding and a transport system play important roles in determining the selectivity of the uptake of PGs by the lung. 相似文献